The specific aim of the proposed research is to map, characterize, and identify by biochemical techniques specific binding sites and subsequent events occurring after binding of vasopressin in the rat brain. By starting from our preliminary results which show the feasibility of vasopressin binding, three major areas of experimental investigation will be further explored. First we shall survey all areas of the rat brain to map those regions where specific binding occurs and then, by use of sucrose gradient centirfugation, we shall identify the subcellular location of this binding. Second, we shall determine the chemical and physical characteristics of this binding by an examination of the metabolic fate of arginine vasopressin during the incubations by HPLC separation techniques, by computations of the dissociation constant of binding by the Scatchard method, by establishment of structure-function relationships between arginine vasopressin and analogues of the hormone by competitive binding techniques, by rate constant determinations for hormone binding, and by examining carefully the role of metal ions in potentiating this binding. And, thirdly, we shall examine a number of possible biochemical events which could occur subsequent to hormone binding. Specifically, we shall examine catecholamine effects, membrane protein and lipid phosphorylation changes, cyclic AMP effects and the possible role of calcium. Although the endocrine effects of vasopressin are well known, the wide distribution of this hormone in the brain as well as some tentative conclusions about the effects of vasopressin on learning and memory suggest that vasopressin may have an important neurological role. These studies are designed to characterize biochemically the nature of the interaction between vasopressin and different regions of the brain. Information obtained from these studies will be directly applicable in explaining the biochemical role of vasopressin in learning and memory, in establishing biochemical correlates for vasopression effects which have been seen following electroshock therapy, and in expanding the pharmacological possibilities of using vasopressin or related peptides in treating premature senility.